Modeled microgravity stimulates osteoclastogenesis and bone resorption by increasing osteoblast RANKL/OPG ratio
Open accessAbstract
Mechanical unloading causes detrimental effects on the skeleton, but the underlying mechanisms are still unclear. We investigated the effect of microgravity on osteoblast ability to regulate osteoclastogenesis. Mouse osteoblast primary cultures were grown for 24 h at unit gravity or under simulated microgravity, using the NASA‐developed Rotating Wall Vessel bioreactor. Conditioned media (CM) from osteoblasts subjected to microgravity increased osteoclastogenesis and bone resorption in mouse bone marrow cultures. In these osteoblasts, the RANKL/OPG ratio was higher relative to 1 g. Consistently, treatment with high concentrations of OPG‐inhibited osteoclastogenesis and bone resorption in the presence of CM arising from osteoblasts cultured under microgravity. Microgravity failed to affect osteoblast differentiation and function in the time frame of the experiment, as we found no effect on alkaline phosphatase mRNA and activity, nor on Runx2, osteocalcin, osteopontin, and collagen1A2 mRNA expression. In contrast, microgravity induced a time dependent increase of ERK‐1/2 phosphorylation, while phospho‐p38 and phospho‐JNK remained unchanged. Apoptosis, revealed by bis‐benzimide staining, was similar among the various gravity conditions, while it was increased under microgravity after treatment with the MEK‐1/2 inhibitor, PD98059, suggesting a protection role by ERK‐1/2 against cell death. In conclusion, microgravity is capable to indirectly stimulate osteoclast formation and activity by regulating osteoblast secretion of crucial regulatory factors such as RANKL and OPG. We hypothesize that this mechanism could contribute to bone loss in individuals subjected to weightlessness and other unloading conditions. J. Cell. Biochem. 100: 464–473, 2007. © 2006 Wiley‐Liss, Inc.
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Conditions of microgravity and simulated microgravity decrease the mineral content and cortical and trabecular microstructures of bone.
“conditions of microgravity and simulated microgravity decrease the mineral content and cortical and trabecular microstructures of bone”
From Osteoclasts and Microgravity (2020) · cites this paper as [65]
The Discussion reports reduced trabecular bone volume, thickness, and number in rats after space flight. The paper also reports increased bone resorption in a simulated-microgravity cell-culture experiment, but it does not establish decreased bone mineral content or cortical microstructure under either condition, or decreased trabecular microstructure under simulated microgravity. (LLM, conf=0.86)
Experimental — accuracy not yet measuredConditions of microgravity and simulated microgravity decrease osteoblastogenesis and osteoblast secretion of OPG.
“decrease osteoblastogenesis and osteoblast secretion of OPG”
From Osteoclasts and Microgravity (2020) · cites this paper as [65]
The Discussion reports that osteoblasts released less OPG under modeled microgravity. It also describes reduced osteoblast differentiation in earlier, longer-duration studies, but this paper found no effect on differentiation after its 24-hour exposure. The unqualified claim that microgravity decreases osteoblastogenesis therefore goes beyond this paper’s own findings. (LLM, conf=0.89)
Experimental — accuracy not yet measuredConditions of microgravity and simulated microgravity increase osteoclast differentiation, fusion, and expression of regulatory and osteoclast-specific genes.
“increase osteoclast differentiation, fusion, and expression of regulatory and osteoclast-specific genes”
From Osteoclasts and Microgravity (2020) · cites this paper as [65]
The 'Effect of Microgravity on Osteoclastogenesis and Bone Resorption' section reports increased osteoclastogenesis in mouse bone-marrow cultures exposed to conditioned medium from osteoblasts grown under modeled microgravity. The Discussion reports an increased osteoblast RANKL/OPG ratio, but our copy does not establish increased osteoclast fusion or expression of osteoclast-specific genes, nor does this experiment test actual microgravity. (LLM, conf=0.88)
Experimental — accuracy not yet measuredSimulated microgravity enhanced osteoclastogenesis by decreasing osteoblast production of OPG, increasing RANKL/OPG ratios.
“The investigators found that simulated microgravity enhanced osteoclastogenesis by decreasing osteoblast production of OPG (increasing RANKL/OPG ratios) [65].”
From Osteoclasts and Microgravity (2020) · cites this paper as [65]
Conditions of microgravity and simulated microgravity increase osteoclast secretion of sclerostin.
“increase osteoclast secretion of sclerostin”
From Osteoclasts and Microgravity (2020) · cites this paper as [65]
The Discussion reports that modeled microgravity changed osteoblast release of OPG and RANKL, stimulating osteoclast differentiation and activity. Neither the provided passages nor searches for sclerostin and SOST address whether microgravity increases osteoclast secretion of sclerostin. (LLM, conf=0.77)
Experimental — accuracy not yet measured
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Smith, J. K. (2020) · Life · doi:10.3390/life10090207 · Cited by 52 · see citing works
- Authors
- Rucci, N., Rufo, A., Alamanou, M., & Teti, A.
- Affiliations
- University of L'Aquila (IT)
- Corresponding author
- Teti, Anna
- Venue
- Journal of Cellular Biochemistry
- Publisher
- Wiley
- Published
- 2006-08-22
- Volume
- 100
- Issue
- 2
- Pages
- 464-473
- ISSN
- 0730-2312 (ISSN-L)
- 1097-4644
- OpenAlex
- W1966550557
- Cited by
- 108
- References
- 0
- Citations by year
- 2026: 3 · 2025: 9 · 2024: 7 · 2023: 6 · 2022: 5 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 4 · 2016: 7 · 2015: 6 · 2014: 4 · 2013: 3 · 2012: 7
- FWCI
- 3.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Cellular Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Archivio Istituzionale della Ricerca - Università degli Studi dell Aquila (submittedVersion)
- Funders
- Agenzia Spaziale Italiana
- Topics
- Health Sciences › Medicine › Physiology › Spaceflight effects on biology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Keywords
- microgravity, osteoclastogenesis, bone resorption, RANKL/OPG ratio, osteoblasts, mechanical unloading, bone loss, rotating wall vessel bioreactor, ERK1/2 phosphorylation, osteoblast apoptosis, conditioned medium
- MeSH terms
- Animals, Bone Resorption, Cell Differentiation, Cells, Cultured, Enzyme Activation, Models, Biological, Osteoclasts, Phenotype, Transcription, Genetic, Weightlessness, Apoptosis, Mitogen-Activated Protein Kinases, Mice, Osteoprotegerin, RANK Ligand
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